In approximately 30% of human breast and prostate cancers, a specific growth factor receptor (ErbB2) is overproduced, resulting in spontaneous receptor dimerization and tyrosine kinase activation. This leads to aggressive uncontrolled growth of tumor cells. The goal of this proposal is to determine the structural basis for ErbB2 dimerization by determining the atomic structure of ErbB2 using x-ray crystallography. Understanding the architectural rules governing growth factor receptor dimerizeration is an essential step towards our long term goal to identify small molecule ErbB2 dimerization antagonists capable of arresting breast cancer growth and understanding the mechanism by which growth factor overexpression leads to unregulated growth. Insights gained into the mechanism of receptor dimerization by analysis of the ErbB2 structure may also be applicable to other members of the EGF family of receptors.